An Open Label Phase 4 Study to Evaluate Efficacy of Early Versus Late Use of Vedolizumab in Ulcerative Colitis

Study Purpose

This multi-centre open label study will involve a minimum of 120 patients in 2 cohorts: 60 patients with 'early UC' defined as disease duration < 4 years and no other treatments than aminosalicylates and/or corticosteroids and 60 patients with 'late UC' defined as active disease despite treatment with immunosuppressives (IS) and/or anti-TNF. Patients wih intolerance to IS AND anti-TNF will also be allowed in the latter group. Participants will be treated with 12 months of open label vedolizumab and undergo monitoring of endoscopic, histological and clinical disease parameters. No randomization or blinding will be performed but the study management will make sure recruitment in either study group is comparable for number and profile of patients (extent of disease and on/off corticosteroids).

Recruitment Criteria

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Accepts Healthy Volunteers
No

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Study Type
Interventional
Eligible Ages 18 Years - 80 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements. 2. The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. Age 18 to 80 4. Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period]). 5. Established diagnosis of ulcerative colitis with histopathological confirmation available in the record of the patient. 6. Moderate to severe active UC (total Mayo score > 6) with objective evidence of inflammation that can be visualized on endoscopy. All endoscopies will be video-taped for later review, rereading and quality assurance. Patients must have an endoscopic Mayo score of 2 or 3. 7. Anti-TNF discontinued for at least 6 weeks 8. Written informed consent must be obtained and documented GROUP 1 (EARLY UC) 1. Diagnosis of UC < 4 years prior to enrollment confirmed by clinical, endoscopic and histopathological evidence. 2. Demonstrated failure to respond to aminosalicylates or intolerance to aminosalicylates and: failure to respond to topical or systemic corticosteroids or intolerance to corticosteroids or: need for > 1 course of steroids per year or: steroid dependency at any dose and additionally, but not mandatory, lack of efficacy of thiopurines or intolerance to thiopurines (azathioprine, 6-mercaptopurine or 6-thioguanine) (any duration). Patients who are using thiopurines at screening must have used them for > 3 months (last 4 weeks at stable dose). GROUP 2 (LATE UC) 1. Diagnosis of UC confirmed by clinical, endoscopic and histopathological evidence. 2. Demonstrated failure to respond to aminosalicylates or intolerance to aminosalicylates and: failure to respond to at least 3 months of thiopurines (TP) or intolerance to TP and: failure to respond to at least 1 anti-TNF or intolerance to anti-TNF or loss of response to at least 1 anti-TNF. Loss of response to anti-TNF is defined as recurrence of symptoms during maintenance dosing following prior clinical benefit. May continue stable dose of conventional therapies for Inflammatory Bowel Disease ( IBD) including aminosalicylates and thiopurines and corticosteroids. Steroids will be tapered by protocol by week 14. Anti-TNF must be discontinued for > 6 weeks.

Exclusion Criteria:

1. Prior treatment with vedolizumab. 2. Contraindication for endoscopy. 3. History of colonic dysplasia/cancer 4. Extensive colonic resection, i.e. subtotal or total colectomy with <15 cm colon remaining 5. Received other biologics within the last 4 weeks of baseline 6. Use of 5-ASA or corticosteroid enemas/suppositories within 2 weeks of enrollment 7. Chronic hepatitis B or C infection 8. Evidence of or treatment for C. difficile infection or other intestinal pathogen at screening within 4 weeks prior to enrollment 9. Active or latent tuberculosis 10. Conditions which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedures. 11. Received any investigational drug in the past 30 days or 5 half-lives, whichever is longer. 12. Positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist before enrollment

Trial Details

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

Trial ID:
NCT02646657

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase
Phase 4

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Lead Sponsor
Geert D'Haens

The person who is responsible for the scientific and technical direction of the entire clinical study.

Principal Investigator
Geert D'Haens, Prof.
Principal Investigator Affiliation Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Agency Class
OtherIndustry
Overall Status Recruiting
Countries Belgium, Hungary, Netherlands

The disease, disorder, syndrome, illness, or injury that is being studied.

Conditions
Colitis, Ulcerative
Additional Details

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Symptoms include bloody diarrhea, weight loss, and fever. There is no known cause or cure for UC. The aim of current UC treatments is to induce and maintain remission, to reduce the need of corticosteroids and avoid colectomy. Treatment options include 5-Aminosalicylates (5-ASA), systemic and/or topical corticosteroids, purine analogues (6-mercaptopurine and azathioprine), anti-TNF antibodies and surgery. In 2013, results from the GEMINI I, phase 3, randomized controlled trial demonstrated the efficacy of vedolizumab (VDZ) in inducing and maintaining remission in adult patients with active UC. VDZ (MLN0002 or MLN02), inhibits the interaction between α4β7 integrin on memory T and B cells and mucosal addressin cell adhesion molecule-1 expressed on the vascular endothelium of the gut and has been shown to be effective in both inducing and maintaining clinical remission in UC. With other (anti-TNF) biologics, outcomes have usually been better if the treatment was started earlier in the disease course and if the patients had not been exposed to prior antibody treatments. Therefore, it appears appropriate and desirable to test the potency of vedolizumab in an earlier phase of UC. Indeed, also with vedolizumab patients previously exposed to biologics appear to have lower success rates with vedolizumab, so a position earlier in the disease course would most likely lead to better outcomes. This is an investigator-initiated open label study of VDZ therapy in 2 distinct populations of UC patients with active disease: 1. patients who have been diagnosed < 4 years ago and who only have been exposed to aminosalicylates and corticosteroids and 2. patients who have been exposed to immunomodulators and/or anti-TNF agents in addition to steroids and aminosalicylates. VDZ has been shown to be efficacious at inducing and maintaining remission in UC. However, data about the endoscopic and histological effects of VDZ in 'early UC' are lacking. Therefore, the investigators propose to perform an interventional study in early and late UC patients including endoscopic and histological assessment

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Erasmus MC, Rotterdam, Netherlands

Status

Recruiting

Address

Erasmus MC

Rotterdam, ,

Radboud UMC, Nijmegen, Netherlands

Status

Recruiting

Address

Radboud UMC

Nijmegen, ,

LUMC, Leiden, Netherlands

Status

Withdrawn

Address

LUMC

Leiden, ,

Catharina ziekenhuis, Eindhoven, Netherlands

Status

Recruiting

Address

Catharina ziekenhuis

Eindhoven, ,

Ziekenhuis Gelderse Vallei, Ede, Netherlands

Status

Recruiting

Address

Ziekenhuis Gelderse Vallei

Ede, ,

OLVG, Amsterdam, Netherlands

Status

Recruiting

Address

OLVG

Amsterdam, ,

Academic Medical Center, Amsterdam, Netherlands

Status

Recruiting

Address

Academic Medical Center

Amsterdam, ,

University of Szeged, Szeged, Hungary

Status

Recruiting

Address

University of Szeged

Szeged, ,

University of Debrechen, Debrecen, Hungary

Status

Recruiting

Address

University of Debrechen

Debrecen, ,

Semmelweis University, Budapest, Hungary

Status

Recruiting

Address

Semmelweis University

Budapest, ,

AZ Delta- Roeselare, Roeselare, Belgium

Status

Recruiting

Address

AZ Delta- Roeselare

Roeselare, ,

AZ Damiaan, Oostende, Belgium

Status

Recruiting

Address

AZ Damiaan

Oostende, ,

ZNA Jan Palfijn, Merksem, Belgium

Status

Recruiting

Address

ZNA Jan Palfijn

Merksem, ,

CHU Liege, Liege, Belgium

Status

Recruiting

Address

CHU Liege

Liege, ,

CHC Clinique Saint-Joseph, Liege, Belgium

Status

Completed

Address

CHC Clinique Saint-Joseph

Liege, ,

Leuven AcademicHospital, Leuven, Belgium

Status

Recruiting

Address

Leuven AcademicHospital

Leuven, ,

Site Contact

Ganel Schops

ganel.schops@uzleuven.be

0031-20 5661125

AZ Groeninge, Kortrijk, Belgium

Status

Recruiting

Address

AZ Groeninge

Kortrijk, ,

UZ Gent, Gent, Belgium

Status

Recruiting

Address

UZ Gent

Gent, ,

AZ Sint-Lucas, Gent, Belgium

Status

Recruiting

Address

AZ Sint-Lucas

Gent, ,

Ziekenhuis Oost-Limburg, Genk, Belgium

Status

Completed

Address

Ziekenhuis Oost-Limburg

Genk, ,

ULB Erasme, Brussels, Belgium

Status

Recruiting

Address

ULB Erasme

Brussels, ,

AZ Sint-Lucas, Brugge, Belgium

Status

Withdrawn

Address

AZ Sint-Lucas

Brugge, ,

Imeldahospital, Bonheiden, Belgium

Status

Recruiting

Address

Imeldahospital

Bonheiden, ,

UZ Antwerpen, Antwerpen, Belgium

Status

Withdrawn

Address

UZ Antwerpen

Antwerpen, ,

St. Vincentius ziekenhuis, Antwerpen, Belgium

Status

Withdrawn

Address

St. Vincentius ziekenhuis

Antwerpen, ,

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